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There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution. In this study, Qin et al. present a murine-adapted SARS-CoV-2 strain, MASCp36, as a model for studying the pathogenicity, evolution and adaptation of the virus to human and animal hosts.

In this paper, we investigate the existence of positive solutions for a system of nonlinear fractional differential equations nonlocal boundary value problems with parameters and p -Laplacian operator. Under different combinations of superlinearity and sublinearity of the nonlinearities, various existence results for positive solutions are derived in terms of different values of parameters via the Guo-Krasnosel’skii fixed point theorem.

In this paper, we are concerned with the existence and uniqueness of solutions for impulsive fractional integro-differential equation of mixed type with constant coefficient and antiperiodic boundary condition. Our results are based on the Banach contraction mapping principle and the Krasnoselskii fixed point theorem. Some examples are also given to illustrate our results.

This article addresses the existence and uniqueness of solution for fully fourth-order differential equations modeling beams on elastic foundations with nonlinear boundary conditions. The proof will rely on Perov’s fixed point theorem in complete generalized metric spaces to overcome the problems due to the presence of all lower-order derivatives in the nonlinearity. Finally, some illustrating examples of the theory are presented.

Records suggest Bacillus anthracis was used in biowarfare during World War II, but evidence remains limited. We isolated B. anthracis from soil at the remains of a World War II-era laboratory in China. Phenotypic and genomic analyses confirmed the finding, highlighting the value of microbial forensics in biothreat investigation.

The authors sequenced the genome of an isolate of E. coli obtained from a German girl with bloody diarrhea and shared the data online with other researchers, facilitating rapid assembly of the genome. Escherichia coli is a widespread commensal of the mammalian gut and a versatile pathogen. 1 , 2 Enterovirulent strains of E. coli are classified into a number of overlapping pathotypes, which include Shiga-toxin–producing, enterohemorrhagic, and enteroaggregative varieties. 2 Enteroaggregative E. coli strains have been associated with sporadic and epidemic diarrhea and, in the laboratory, show a distinctive pattern of adherence to Hep-2 cells (termed aggregative, or “stacked brick”). 3 In Shiga-toxin–producing E. coli, the toxin is encoded on a prophage and inhibits protein synthesis within susceptible eukaryotic cells. Strains of enterohemorrhagic E. coli produce Shiga toxin and a specific protein secretion system (called a . . .

In this article, by using topological degree theory couple with the method of lower and upper solutions, we study the existence of at least three solutions to Riemann-Stieltjes integral initial value problem of the type Dαx(t)=f(t,x), t∈[0,1], x(0)=∫01x(t)dA(t), where Dαx(t) is the standard conformable fractional derivative of order α, 0<α≤1, and f∈C([0,1]×R,R). Simultaneously, the fixed point theorem for set-valued increasing operator is applied when considering the given problem.

In this paper, we focus on the convergence analysis and error estimation for the unique solution of a p-Laplacian fractional differential equation with singular decreasing nonlinearity. By introducing a double iterative technique, in the case of the nonlinearity with singularity at time and space variables, the unique positive solution to the problem is established. Then, from the developed iterative technique, the sequences converging uniformly to the unique solution are formulated, and the estimates of the error and the convergence rate are derived.

Yersinia pestis is transmitted from fleas to rodents when the bacterium develops an extensive biofilm in the foregut of a flea, starving it into a feeding frenzy, or, alternatively, during a brief period directly after feeding on a bacteremic host. These two transmission modes are in a trade-off regulated by the amount of biofilm produced by the bacterium. Here by investigating 446 global isolated Y. pestis genomes, including 78 newly sequenced isolates sampled over 40 years from a plague focus in China, we provide evidence for strong selection pressures on the RNA polymerase ω-subunit encoding gene rpoZ . We demonstrate that rpoZ variants have an increased rate of biofilm production in vitro, and that they evolve in the ecosystem during colder and drier periods. Our results support the notion that the bacterium is constantly adapting—through extended phenotype changes in the fleas—in response to climate-driven changes in the niche. Yersinia pestis , the causative agent of plague, can change its biofilm production to influence the dynamics of flea-borne transmission. Here, the authors sequence Y. pestis isolates sampled over 40 years in China and show evidence for climate-associated selection on rpoZ to increase biofilm production.